Septic shock during invasive bacterial infection is one of the most common causes of morbidity and mortality in patients in medical intensive care units (ICUs). Despite the use of effective antibiotics in combination with cardiovascular support (therapy to increase blood pressure), the mortality rate with septic shock remains high (29%). Myocardial (heart) dysfunction is an important contributor to the pathogenesis of shock during sepsis. Understanding the nature of this dysfunction and its treatment will be important for the management of sepsis in the future. Relevant animal models will greatly aid in such research. Although the mouse is one of the most frequently employed animal species for the study of sepsis, a recent literature review has shown that myocardial dysfunction in this model has received little attention. In fact, only one published study has assessed myocardial changes in a bacteria challenged mouse sepsis model. The goals of the present study have been to employ echocardiography (organ imaging with sound waves), pressure-conductance techniques (pressure and volume measures using electrical conductance measures or PV-measures) and gene microarray analysis to define the pattern of myocardial dysfunction occurring during E. coli pneumonia in mice. Since several factors such as the severity of infection itself as well as the presence or absence of conventional hemodynamic support vary in patients clinically, their influence on myocardial function in this mouse model will be assessed as well. Initial experiments have been completed. First using recognized positive and negative inotropic agents (dobutamine and esmolol respectively) it was possible to show that pressure-conductance measures could be effectively applied in our murine model. Subsequent experiments have demonstrated the effects of intratracheal E. coli challenge on myocardial function. Similar to what occurs is humans, at both 24 and 48 h after E. coli challenge, contractility was reduced based on reductions in preload recruitable stroke work and the dP/dtmax -end-diastolic volume relationship. In studies now underway, cardiac echocardiography (previously developed for this model), pressure-conductance measures, and gene microarray analysis will be employed, along with tissue immunohistochemistry and electron microscopy to further characterize the myocardial changes associated with E. coli pneumonia and the influence severity of septic challenge (i.e. changing bacteria dose) and conventional hemodynamic support (i.e fluid support) might have on these changes.